The synthesis of chemically modified disaccharide derivatives of the Shigella flexneri Y polysaccharide antigen

Abstract

Disaccharide analogs related to the 2-acetamido-2-deoxy-3- O(α- l-rhamnopyranosyl)-β- d-glucopyranose element of the Shigella flexneri Y polysaccharide antigen have been synthesized and used to map the binding site of murine monoclonal antibodies GC-4 and SYA/J6 by solid-phase inhibition assays. N-Acetyl, N-trifluoroacetyl and N-benzyloxycarbonyl derivatives of methyl 2-amino-4,6- O-benzylidene-2-deoxy-β- d-glucopyranoside 1, 3 and 4 were glycosylated by rhamnopyranosyl bromide and thioglycoside donors 5 and 6. These in turn provided access to a series of α- l-Rha p-(1 → 3)-β- d-GlcN p-(1 → O)-Me disaccharide glycosides with amino 13, N-acetyl 10, N-propionyl 14, N-pivaloyl 15, and N-trifluoroacetyl 11 functionalities. Congeners of the disaccharide 10 were synthesized with monodeoxy groups introduced at the C-4 and C-6 positions of the GlcNAc residues and at the C-4′ position of the rhamnose unit. Chlorosulfation of the selectively protected disaccharide 24, followed by reduction of the 4-chloro-4-deoxy compound 25, was used to prepare the 4-deoxy congener 27, while the C-6 and C-4′ deoxy derivatives 31 and 23 were assembled from their respective pre-functionalized monosaccharide building blocks 29 and 19.